Association of human cytomegalovirus infection and cytokine dysregulation with recurrent spontaneous miscarriage

Background: An imbalance of cytokines and the maternal immune response is associated with recurrent spontaneous miscarriages (RSM). Therefore, this study investigates the relationship between HCMV infection, the expression of interferon-gamma (IFN-γ) and interleukin-2 (IL-2) genes, and the risk of RSM in pregnant women. Methods: Blood samples were collected from a total of 64 participants, including 40 women who had RSM and 24 age-matched healthy controls. ELISA was utilized to test serum for HCMV- IgM and IgG. RT-qPCR was used to quantify the mRNA levels of IL-2 and IFN-γ. Vaginal and cervical swabs were used for the molecular diagnosis of HCMV, targeting two viral genes: the immediate-early gene 2 (IE2) and glycoprotein B (gB). Results: Serological analysis demonstrated significantly higher anti-HCMV IgG antibodies in the miscarriage group compared to the controls (100% vs 37.5%, p < 0.0001). Moreover, 20% of the miscarriage group had detectable IgM antibodies. In the miscarriage group, IFN-γ and IL-2 mRNA levels were downregulated 2.6-fold (p < 0.0001) and 1.9-fold (p < 0.0012), respectively. The two viral genes, IE2 and gB, were successfully amplified, yielding 72-bp and 92-bp bands, respectively. Conclusion: The data suggest that past or reactivated HCMV infection may be associated with RSM, as indicated by the detection of viral genes and a reduction in Th1-type cytokine expression. These results highlight the potential impact of viral infections and immune system dysregulation in RSM, prompting the need for novel diagnostic and therapeutic approaches. Further studies are necessary to confirm these findings and clarify the underlying mechanisms.